System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print

PubMed: 41192697 DOI: 10.1016/j.bbi.2025.106161

Gut microbiome-derived tryptophan metabolites predict relapse in alcohol use disorder.

Brain Behav Immun

Authors: Cameron Forton, Jack DeVries, Miles Lou, Samuel Brundin, Tyce Cave, Ehraz Anis, Zach Madaj, Christine Isaguirre, Amy Johnson, Ryan D Sheldon, LeAnn Smart, Kipling M Bohnert, Janelle Kassien, Olivia Holzgen, Nagy A Youssef, Talal Khan, Lena Brundin

Affiliations

  • Dept. of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • University of San Diego, San Diego, CA, USA.
  • East Grand Rapids Public Schools, East Grand Rapids, MI, USA.
  • Dept. of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.
  • Bioinformatics & Biostatistics Core, Van Andel Institute, Grand Rapids, MI, USA.
  • Mass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA.
  • Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA.
  • Dept. of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, USA.
  • Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA; College of Human Medicine, Michigan State University, East Lansing, MI, USA.

Abstract

Relapse is common in alcohol use disorder (AUD), a condition that affects nearly 11 % of adults in the US. Excessive alcohol consumption causes gut dysbiosis, which may in turn alter the production of bacterial-derived tryptophan metabolites. These metabolites impact the intestinal enteroendocrine environment and modulate neuroinflammation. This can ultimately affect behavior. However, the role of bacterial-derived tryptophan metabolites in AUD is not well-understood. Thus, in this study, we enrolled 40 patients admitted for severe AUD (26 males, 14 females) to investigate whether bacterial-derived indoles could predict AUD relapse. Upon enrollment, alcohol use as well as depression and anxiety symptoms were assessed. Peripheral blood samples were collected and analyzed for cytokines, bacterial-derived as well as endogenous tryptophan metabolites, and hematological factors. At three months after discharge, 25 patients completed follow-up and were re-assessed for clinical symptoms to identify AUD relapse. Ten patients relapsed and 15 patients were in early remission. Two bacterial tryptophan metabolites, indole-3-carboxaldehyde (IAld) and indole-3-acetic acid (IAA), significantly predicted relapse versus remission using logistic regression models (p = 0.019, SGPV = 0, and p = 0.035, SGPV = 0 respectively). These findings remained significant after adjustment for age, sex, BMI, and when additionally adjusting for nicotine use and depression severity. Moreover, higher IAld levels correlated with increased serotonin levels (Pearson's R; 0.592, p < 0.001) and fewer white blood cells (Pearson's R; -0.318, p < 0.05) in all 40 patients. Our data indicate significant interactions between microbiome-derived metabolites and host metabolism, and that IAld specifically may have a protective role in AUD, potentially through serotonin modulation.

MeSH

Depression, Blood, Alcoholism, Tryptophan, Signs And Symptoms, Serotonin, Gastrointestinal Microbiome